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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

FUMONISIN B1
(Group 2B)

For definition of Groups, see Preamble Evaluation.

VOL.: 82 (2002) (p. 301)

CAS No.: 116355-83-0

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Fumonisin B1 is the most prevalent member of a family of toxins produced by several species of Fusarium moulds which occur mainly in maize. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

5.2 Human carcinogenicity data

No new studies on the human carcinogenicity of fumonisins were available to the Working Group.

5.3 Animal carcinogenicity data

Fumonisin B1 has been tested for carcinogenicity by oral administration in one study in mice, one study in male rats and one study in male and female rats. In female mice, it caused an increase in hepatocellular adenomas and carcinomas. In one study in male rats, it caused an increase in cholangiocarcinomas and hepatocellular carcinomas. In the other rat study, it induced renal tubule carcinomas in male rats, over half of which were classified as a rare highly malignant variant.

Fumonisin B1 has also been shown to promote tumours in mouse skin and trout livers when 7,12-dimethylbenz[a]anthracene and aflatoxin B1, respectively, were used as tumour initiators.

5.4 Other relevant data

Fumonisins are poorly absorbed, rapidly excreted and not metabolized in animal systems. The half-life for elimination in animal species is directly related to the average body weight of the species, suggesting that the half-life in humans will be longer than those determined experimentally in rats and other animals.

Fumonisin B1 is hepatotoxic and nephrotoxic in all animal species tested. The earliest histological change to appear in either the liver or kidney of fumonisin-treated animals is increased apoptosis followed by regenerative cell proliferation. While the acute toxicity of fumonisin is low, it is the known cause of two diseases which occur in domestic animals with rapid onset: equine leukoencephalomalacia and porcine pulmonary oedema syndrome. Both of these diseases involve disturbed sphingolipid metabolism and cardiovascular dysfunction.

Fumonisin B1 causes developmental toxicity in several animal species. In rats, mice and rabbits, developmental effects occurred at dose levels associated with disruption of sphingolipid metabolism and maternal toxicity in liver and kidney.

Postnatal dosing causes decreased survival of rat pups and results indicate that sphingolipid metabolism is vulnerable after birth.

Fumonisin B1 is inactive in bacterial mutation assays and in the unscheduled DNA synthesis assay with rat hepatocytes, but induces DNA damage, such as micronuclei, in vitro and in vivo. In some studies, addition of antioxidants reduced the DNA-damaging effects of fumonisin B1, suggesting that the effects may be due to oxidative stress.

Disruption of various aspects of lipid metabolism, membrane structure and signal transduction pathways mediated by lipid second messengers appears to be an important aspect of all the various proposed mechanisms of action of fumonisin B1, including its mechanism of carcinogenicity.

Fumonisin B1-induced disruption of sphingolipid, phospholipid and fatty acid metabolism is observed both in vitro and in vivo in all animal models and in a single human study. Disruption of sphingolipid metabolism by fumonisin B1 in animal and human systems in vitro causes cell death and regenerative cell proliferation mediated through sphingolipid signalling pathways. The kinetics of the increases and decreases in the various bioactive sphingolipid pools in liver, kidney, lung and heart are correlated with the observed toxicity.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of fumonisins.

There is sufficient evidence in experimental animals for the carcinogenicity of fumonisin B1.

Overall evaluation

Fumonisin B1 is possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

Synonyms


Last updated: 4 December 2002


    See Also:
       Toxicological Abbreviations
       Fumonisin B1 (EHC 219, 2000)